Hyperthyroidism – Causes, Symptoms, Diagnosis, Treatment

Hyperthyroidism is a condition that occurs due to excessive production of thyroid hormone by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism. Some, however, use the terms interchangeably. Signs and symptoms vary between people and may include irritability, muscle weakness, sleeping problems, a fast heartbeat, heat intolerance, diarrhea, enlargement of the thyroid, and weight loss. Symptoms are typically less in the old and during pregnancy. An uncommon complication is a thyroid storm in which an event such as an infection results in worsening symptoms such as confusion and a high temperature and often results in death. The opposite is hypothyroidism when the thyroid gland does not make enough thyroid hormone

Causes of Hyperthyroidism

The major causes in humans are

• Graves’ disease. An autoimmune disease (usually, the most common etiology with 50-80% worldwide, although this varies substantially with location- i.e., 47% in Switzerland (Horst et al., 1987) to 90% in the USA (Hamburger et al. 1981)). Thought to be due to varying levels of iodine in the diet. It is eight times more common in females than males and often occurs in young females, around 20 – 40 years of age.
• Toxic thyroid adenoma (the most common etiology in Switzerland, 53%, thought to be atypical due to a low level of dietary iodine in this country)
• Toxic multinodular goiter

High blood levels of thyroid hormones (most accurately termed hyperthyroxinemia) can occur for a number of other reasons

• Inflammation of the thyroid is called thyroiditis. There are several different kinds of thyroiditis including Hashimoto’s thyroiditis (Hypothyroidism immune-mediated), and subacute thyroiditis (de Quervain’s). These may be initially associated with secretion of excess thyroid hormone but usually progress to gland dysfunction and, thus, to hormone deficiency and hypothyroidism.
• Oral consumption of excess thyroid hormone tablets is possible (surreptitious use of thyroid hormone), as is the rare event of consumption of ground beef contaminated with thyroid tissue, and thus thyroid hormone (termed “hamburger hyperthyroidism”). Pharmacy compounding errors may also be a cause.
• Amiodarone, an antiarrhythmic drug, is structurally similar to thyroxine and may cause either under-or overactivity of the thyroid.
• Postpartum thyroiditis (PPT) occurs in about 7% of women during the year after they give birth. PPT typically has several phases, the first of which is hyperthyroidism. This form of hyperthyroidism usually corrects itself within weeks or months without the need for treatment.
• A struma ovarii is a rare form of monodermal teratoma that contains mostly thyroid tissue, which leads to hyperthyroidism.
• Excess iodine consumption notably from algae such as kelp.

Thyrotoxicosis can also occur after taking too much thyroid hormone in the form of supplements, such as levothyroxine (a phenomenon known as exogenous thyrotoxicosis, alimentary thyrotoxicosis, or occult factitial thyrotoxicosis).

Hypersecretion of thyroid-stimulating hormone (TSH), which in turn is almost always caused by a pituitary adenoma, accounts for much less than 1 percent of hyperthyroidism cases.

Symptoms of Hyperthyroidism

Signs of Hyperthyroidism

Symptoms of Hyperthyroidism

Generalized hypermetabolism from hyperthyroidism causes increased Na+/K+-ATPase to promote thermogenesis. There is increased catecholamine secretion and, beta-adrenergic receptors are also upregulated in various tissues. As a result of the hyperadrenergic state, peripheral vascular resistance is decreased. In the heart, hyperthyroidism causes a decreased amount of phospholamban, a protein that normally decreases the affinity of calcium-ATPase for calcium in the sarcoplasmic reticulum. As a result of decreased phospholamban, there is increased Ca+ movement between the sarcoplasmic reticulum and cytosol, leading to increased contractility. Increased beta-receptors on the heart also lead to increased cardiac output.

General

• Rapid pulse
• Elevated blood pressure
• Protruding eyes
• Enlarged thyroid gland
• Heat intolerance
• Weight loss
• Increased appetite
• Increased sweating from cutaneous blood flow increase
• Weakness
• Fatigue
• Onycholysis (separation of nails from nail beds)
• Pretibial myxedema

Eyes

• Lid lag (when looking down, sclera visible above cornea)
• Lid retraction (when looking straight, sclera visible above the cornea)
• Graves ophthalmopathy

Goiter

• Diffuse, smooth, non-tender goiter
• The audible bruit can be heard at the superior poles

Cardiovascular

• Tachycardia (can be masked by patients taking beta-blockers)
• Palpitations
• An irregular pulse from atrial fibrillation
• Hypertension
• Widened pulse pressure because systolic pressure increases and diastolic pressure decreases
• Heart failure (elderly patients)
• Chest pain
• Abnormal heart rhythms

Musculoskeletal

• Fine tremors of the outstretched fingers. Face, tongue, and head can also be involved. Tremors respond well to treatment with beta-blockers.
• Myopathy affecting proximal muscles. Serum creatine kinase levels can be normal
• Osteoporosis caused by the direct effects of T3. Elderly patients can present with fractures.

Neuropsychiatric system

• Restlessness
• Anxiety
• Depression
• Emotional instability
• Insomnia
• Tremoulousness
• Hyperreflexia

Conditions associated with hypothyroidism

• Iodine deficiency
• Cretinism
• Wolff-Chaikoff effect
• Subacute thyroiditis
• Postpartum thyroiditis
• Riedel thyroiditis
• Hashimoto thyroiditis
• Drug-induced [rx]

Conditions associated with hyperthyroidism

• Graves disease
• Iodine excess
• Struma ovarii
• Thyrotropic pituitary adenoma
• Jod-Basedow phenomenon
• Drug-induced: amiodarone, lithium
• Thyrotoxicosis and thyroid storm
• Toxic multinodular goiter [rx]
• Thyroid adenoma [rx]

Scoring (Burch, Wartofsky)

• >45: thyroid storm
• 25-44: impending thyroid storm
• <25: unlikely thyroid storm

Other tests may be performed to further evaluate your diagnosis. These include:

• Cholesterol test – Your doctor may need to check your cholesterol levels. Low cholesterol can be a sign of an elevated metabolic rate, in which your body is burning through cholesterol quickly.
• T4, free T4, T3 – These tests measure how much thyroid hormone (T4 and T3) is in your blood.
• Thyroid-stimulating hormone level test – Thyroid-stimulating hormone (TSH) is a pituitary gland hormone that stimulates the thyroid gland to produce hormones. When thyroid hormone levels are normal or high, your TSH should be lower. An abnormally low TSH can be the first sign of hyperthyroidism.
• Triglyceride test – Your triglyceride level may also be tested. Similar to low cholesterol, low triglycerides can be a sign of an elevated metabolic rate.
• Thyroid scan and uptake – This allows your doctor to see if your thyroid is overactive. In particular, it can reveal whether the entire thyroid or just a single area of the gland is causing the overactivity.
• Ultrasound – Ultrasounds can measure the size of the entire thyroid gland, as well as any masses within it. Doctors can also use ultrasounds to determine if a mass is solid or cystic.
• CT or MRI scans – A CT or MRI can show if a pituitary tumor is present that’s causing the condition.

Treatment

The long-term outlook for hyperthyroidism depends on its cause. Some causes can go away without treatment.

Supportive measures

• Volume resuscitation and cooling
• Benzodiazepines for agitation

Beta-blockade

• Propranolol 60-80mg PO q4h
• Propranolol 0.5-1.0mg IV, repeat q15min then 1-2mg q3h
• Esmolol continuous infusion

Antithyroid drugs 

Antithyroid drugs that work in the thyroid gland

• Perchlorate – inhibits Na+/I- symporter – blocks iodide uptake
• Thionamides – inhibits TPO – block thyroid hormone synthesis
• Iodide > 5mg – inhibits Na+/I- symporter and TPO – blocks iodide uptake and thyroid hormone synthesis
• Lithium – inhibits thyroid hormone release (off-label use for thyroid storm)

Antithyroid drugs that work in peripheral tissue – all these drugs inhibit the deiodinase enzymes. Deiodinase enzymes normally convert T4 into the active form T3. These drugs inhibit the conversion of T4 to T3 and reduce its activity.

• Propylthiouracil (ethionamide)
• Dexamethasone
• Amiodarone
• Propranolol
• Thermostatic (antithyroid drugs) are drugs that inhibit the production of thyroid hormones, such as carbimazole (used in the UK) and methimazole (used in the US, Germany, and Russia), and propylthiouracil. Thyrostatics are believed to work by inhibiting the iodination of thyroglobulin by thyroperoxidase and, thus, the formation of tetraiodothyronine (T₄).
• Propylthiouracil also works outside the thyroid gland, preventing the conversion of (mostly inactive) T₄ to the active form T₃. Because thyroid tissue usually contains a substantial reserve of thyroid hormone, hydrostatics can take weeks to become effective and the dose often needs to be carefully titrated over a period of months, with regular doctor visits and blood tests to monitor results.
• Antithyroid medications, such as methimazole (Tapazole), stop the thyroid from making hormones. They are a common treatment.
• Radioactive iodine is given to over 70 percent of U.S. adults with hyperthyroidism, according to the American Thyroid Association. It effectively destroys the cells that produce hormones.

Hyperthyroidism can also cause your bones to become weak and thin, which can lead to osteoporosis. Taking vitamin D and calcium supplements during and after treatment can help strengthen your bones. Your doctor can tell you how much vitamin D and calcium to take each day.

Your doctor may refer you to an endocrinologist, who specializes in treating bodily hormone systems. Stress or infections can cause thyroid storms. A thyroid storm happens when a large amount of thyroid hormone is released and it results in a sudden worsening of symptoms. Treatment is important to prevent thyroid storms, thyrotoxicosis, and other complications.

Beta-blockers

Many of the common symptoms of hyperthyroidism such as palpitations, trembling, and anxiety is mediated by increases in beta-adrenergic receptors on cell surfaces. Beta-blockers, typically used to treat high blood pressure, are a class of drugs that offset this effect, reducing rapid pulse associated with the sensation of palpitations, and decreasing tremor and anxiety.

Some minimal effect on thyroid hormone production however also comes with Propranolol – which has two roles in the treatment of hyperthyroidism, determined by the different isomers of propranolol. L-propranolol causes beta-blockade, thus treating the symptoms associated with hyperthyroidism such as tremors, palpitations, anxiety, and heat intolerance. D-propranolol inhibits thyroxine deiodinase, thereby blocking the conversion of T₄ to T₃, providing some though minimal therapeutic effect. Other beta-blockers are used to treat only the symptoms associated with hyperthyroidism. Propranolol in the UK, and Metoprolol in the US, are most frequently used to augment treatment for hyperthyroid patients.

Diet

People with autoimmune hyperthyroidism should not eat foods high in iodine, such as edible seaweed and kelps. From a public health perspective, the general introduction of iodized salt in the United States in 1924 resulted in lower disease, goiters, as well as improving the lives of children whose mothers would not have eaten enough iodine during pregnancy which would have lowered the IQs of their children.

Surgery

Surgery (thyroidectomy to remove the whole thyroid or a part of it) is not extensively used because most common forms of hyperthyroidism are quite effectively treated by the radioactive iodine method, and because there is a risk of also removing the parathyroid glands, and of cutting the recurrent laryngeal nerve, making swallowing difficult, and even simply generalized staphylococcal infection as with any major surgery. Some people with Graves’ may opt for surgical intervention. This includes those that cannot tolerate medicines for one reason or another, people that are allergic to iodine, or people that refuse radioiodine.

If people have toxic nodules treatments typically include either removal or injection of the nodule with alcohol.

Radioiodine

In iodine-131 (radioiodine) radioisotope therapy, which was first pioneered by Dr. Saul Hertz, radioactive iodine-131 is given orally (either by pill or liquid) on a one-time basis, to severely restrict, or altogether destroy the function of a hyperactive thyroid gland. This isotope of radioactive iodine used for ablative treatment is more potent than diagnostic radioiodine (usually iodine-123 or a very low amount of iodine-131), which has a biological half-life from 8–13 hours. Iodine-131, which also emits beta particles that are far more damaging to tissues at short range, has a half-life of approximately 8 days. Patients not responding sufficiently to the first dose are sometimes given an additional radioiodine treatment, at a larger dose. Iodine-131 in this treatment is picked up by the active cells in the thyroid and destroys them, rendering the thyroid gland mostly or completely inactive.

Common Questions Frequently Asked By Patients

References

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